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Antiangiogenic activity of herboxidiene via downregulation of vascular endothelial growth factor receptor-2 and hypoxia-inducible factor-1α

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Abstract

Antiangiogenesis is now thought of as one of the most important approaches for anticancer therapy. In this study, we determined the antiangiogenic property of herboxidiene, a polyketide natural product. Herboxidiene effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) at concentrations not exhibiting cytotoxicity. Furthermore, the natural product significantly suppressed vascular endothelial growth factor-induced invasion and tube formation in HUVECs as well as neovascularization of the chorioallantoic membrane in developing chick embryos. We also identified an association between the antiangiogenic activity of herboxidiene and the downregulation of both the phosphorylation of VEGF receptor 2 (KDR/Flk-1) and the expression of hypoxia-inducible factor-1α at the transcriptional level. These results suggest that herboxidiene functions as a potential antiangiogenic agent and may be applicable for anticancer therapy by targeting tumor angiogenesis.

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Acknowledgments

This study was partly supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean Government (2010-0017984 and 2012M3A9D1054520), the Translational Research Center for Protein Function Control, KRF (2009-0083522), the Ministry of Health & Welfare (0620360-1), the Basic Science Research Program, the Ministry of Education (NRF-2014R1A1A2057902), and the Brain Korea 21 Plus Project, Republic of Korea.

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    Authors and Affiliations

    1. Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, 70, Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam, 336-708, Republic of Korea

      Hye Jin Jung, Ju Yong Shin & Jae Kyung Sohng

    2. Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-749, Republic of Korea

      Yonghyo Kim & Ho Jeong Kwon

    3. Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, 120-752, Republic of Korea

      Ho Jeong Kwon

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    1. Hye Jin Jung
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    2. Yonghyo Kim
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    Correspondence to Ho Jeong Kwon.

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    Hye Jin Jung and Yonghyo Kim contributed equally to this work.

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    Jung, H.J., Kim, Y., Shin, J.Y. et al. Antiangiogenic activity of herboxidiene via downregulation of vascular endothelial growth factor receptor-2 and hypoxia-inducible factor-1α. Arch. Pharm. Res. 38, 1728–1735 (2015). https://doi.org/10.1007/s12272-015-0625-4

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